Maturational differences in lung NF-kappaB activation and their role in tolerance to hyperoxia.
Maturational differences in lung NF-kappaB activation and their role in tolerance to hyperoxia.
复制标题
肺 NF-κB 激活的成熟差异及其在高氧耐受性中的作用。
DOI：
10.1172/jci19300
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Dennery,PhyllisA
中科院分区：
文献类型：
--
作者：
Yang,Guang;Abate,Aida;George,AdiaG;Weng,Yi-Hao;Dennery,PhyllisA
新生啮齿动物比成年啮齿动物更能耐受高氧。我们确定了肺NF-κB激活的成熟差异是否可以解释这种差异。高氧暴露（O2浓度95%）后，新生儿（<12小时）肺NF-κB结合增加，并在8 - 16小时达到最大值，而成人没有观察到变化。此外，新生儿NF-κB/荧光素酶转基因小鼠（包含2个驱动荧光素酶基因表达的NF-κB共识序列）在高氧后实时显示体内NF-κB活化增强。新生儿肺部有NF-κB活化的倾向，表现为肺I-κB激酶蛋白水平升高、I-κBα磷酸化、β-转导蛋白重复序列蛋白水平升高以及I-κBα总降解。p-JNK免疫反应蛋白仅在成人肺中升高。bae11 -7085抑制pI-κBα导致高氧暴露后新生儿肺匀浆中Bcl-2蛋白水平降低，肺原代培养细胞活力降低。此外，与WT小鼠相比，新生p50-零突变（p50 - / -）小鼠在高氧条件下肺DNA降解增加，存活率降低。这些数据表明，肺NF-κB的激活存在成熟差异，NF-κB的增强可能通过抑制细胞凋亡来保护新生儿肺免受急性高氧损伤。
Neonatal rodents are more tolerant to hyperoxia than adults. We determined whether maturational differences in lung NF-κB activation could account for the differences. After hyperoxic exposure (O2> 95%), neonatal (<12 hours old) lung NF-κB binding was increased and reached a maximum between 8 and 16 hours, whereas in adults no changes were observed. Additionally, neonatal NF-κB/luciferase transgenic mice (incorporating 2 NF-κB consensus sequences driving luciferase gene expression) demonstrated enhanced in vivo NF-κB activation after hyperoxia in real time. In the lungs of neonates, there was a propensity toward NF-κB activation as evidenced by increased lung I-κB kinase protein levels, I-κBα phosphorylation, β-transducin repeat–containing protein levels, and total I-κBα degradation. Increased lung p-JNK immunoreactive protein was observed only in the adult lung. Inhibition of pI-κBα by BAY 11-7085 resulted in decreased Bcl-2 protein levels in neonatal lung homogenates and decreased cell viability in lung primary cultures after hyperoxic exposure. Furthermore, neonatal p50-null mutant (p50–/–) mice showed increased lung DNA degradation and decreased survival in hyperoxia compared with WT mice. These data demonstrate that there are maturational differences in lung NF-κB activation and that enhanced NF-κB may serve to protect the neonatal lung from acute hyperoxic injury via inhibition of apoptosis.